Epilepsy is one of the most common disorders of the central nervous system and there are over 50 million sufferers in the world. According to the definition by WHO, epilepsy is “a chronic brain disease of various etiologies characterized by recurrent seizures (epileptic seizures) due to excessive discharges of cerebral neurons, accompanied by a variety of clinical and laboratory manifestations”.
As epileptic seizures, for example, partial seizures such as simple partial seizures, complex partial seizures and secondary generalized seizures, absence seizures, myoclonic seizures, tonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures, atonic seizures, West syndrome and Lennox-Gastaut syndrome are known.
The mainstream of treatment of the epilepsy is pharmacotherapy with antiepileptic drugs (AED). The goal of treating epilepsy is to abolish seizures and to prevent side effects during treatment. Treatment by antiepileptic drugs is initiated from a single drug in principle.
The single drug therapy is usually tried by two or three kinds of drugs in turn. If monotherapy is not successful, polytherapy is used. In about 70% of patients with new on-set epilepsy, remission of seizures is expected by monotherapy.
It is known that, however, in the remaining 30 percent of those, pharmacotherapy including polytherapy cannot control their epileptic seizures.
Examples of launched antiepileptic drugs are carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, sodium valproate, zonisamide, felbamate, gabapentine, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, eslicarbazepine, pregabalin, lacosamide, rufinamide, trimethadione, sultiame, acetazolamide, vigabatrin, benzodiazepine derivatives (clonazepam, clobazam, nitrazepam, diazepam), perampanel, retigabine, etc (Non Patent Literature 1).
These known antiepileptic drugs exert an effect by inhibiting neuronal hyperexcitability.
One of the serious problems in therapy by antiepileptic drugs is toxicity due to their inhibitory effect on neurologic function (dizziness, nystagmus, ambiopia, drowsiness, emesis, ataxia, psychological symptom, tiredness and evolition, etc.).
These are side effects that most of these conventional antiepileptic drugs have in a dose-dependent manner, and these are serious problems that lead to limit choice of the therapeutic agents and their dose.
The side effects also worsen the quality of life of epilepsy patients in need of long-term dosing.
Thus, the drugs that are superior in difference between effective dose and neurotoxic doses are in demand.
As 1-indansufamides, the low-molecular compounds in the following Patent Literature 1 and 2, and Non Patent Literature 2 are known.